The Council of Independent Colleges (CIC) is an association in the United States of more than 650 independent, liberal arts colleges and universities and more than 100 higher education affiliates and organizations that work together to strengthen college and university leadership, sustain high-quality education, and enhance private higher education’s contributions to society. To fulfill its mission, CIC provides ideas, resources, and programs that help institutions improve their leadership expertise, educational programs, administrative and financial performance, and institutional visibility. Member institutions are drawn from across the spectrum of independent higher education, including selective liberal arts colleges, medium-sized private universities, religious colleges, historically black colleges, and single-sex institutions. The Council is headquartered at One Dupont Circle in Washington, DC.
Although enzyme immobilization is widely used in biotechnology, it still poses challenges as a result of the trade-offs among stability, activity, and surface interactions. Computer simulations offer a promising aid to exploring the effects of different immobilization sites and surface chemistry on both the conformational dynamics and catalytic activity of these biomolecules. Here, we introduce a protocol based on a structure-based version of the Martini coarse-grained simulation model (Go̅Martini) to explore how surface tethering geometry influences the structure and function of immobilized Bacillus stearothermophilus alcohol dehydrogenase (BsADH). We compare traditional His-tag tethering with two engineered histidine cluster variants, analyzing their behavior in both soluble and surface-tethered states. We find that cluster-based immobilization locally restricts flexibility in surface-contacting subunits while preserving the mobility of exposed regions, resulting in an enhanced conformational stability under thermal stress. Functional analyses reveal that the ethanol association rates remain largely unaffected by surface attachment, whereas the dissociation of NADH is significantly slowed, explaining the reduced catalytic efficiency. These trends align with experimental findings and highlight the predictive power of Go̅Martini simulations in capturing key functional trade-offs. Altogether, this work offers mechanistic insight into the rational design of immobilized biocatalysts and outlines a practical framework for in silico exploration of enzyme-surface systems.
Pristine carbon nanotubes (CNTs) have proven to be excellent supports for cardiac cell growth, survival and maturation, as well to improve cellular function, enhance spontaneous beating activity and benefit their cellular structure. Due to the large quantity of cardiomyocytes that have to be replaced for myocardial regeneration, iPSCs are the most promising candidates for robust generation of cardiomyocytes in vivo/vitro. Herein, iPSCs are cultured and differentiated into cardiomyocytes on functionalized carbon nanotubes (fCNTs). For this purpose, a first optimization of the type of plate and the number of iPSCs suitable for the passaging is performed. Thus, 500.000 cells per cm2 are cultured in 24-well and 8-well plates. After 19-days of differentiation and maturation, calcium imaging was done to analyze the spontaneous beating behavior by means of beat frequency and amplitude, immunofluorescence was done to observe evaluate the degree of maturation by staining the sarcomere and the cell nucleus. A set of diverse functionalized CNTs were also tested: pristine CNT, ox-CNT, CNT-COOH, CNT-NH2, CNT-NO2 and CNT-SO3. Calcium analysis showed that all but the nitro-functionalization were beating, with acid-and oxygen derivative CNTs producing an increase in frequency with respect to control, while amino-functional groups decrease it. This suggests that the beating and contractile behavior of cardiomyocyte can be modulated according to the cardiac issue to be faced. In addition, CNT-SO3 produces a striated and elongated sarcomere, proper of the real tissue. ### Competing Interest Statement The authors have declared no competing interest. Spanish State Research Agency, MDM-2017-0720, MCIN/AEI/10.13039/501100011033, PID2022-140419OB-I00, CNS2024-154900 European Commission, ERC-2024-POC, grant agreement no. 101213598 La Caixa Foundation Spanish National Plan for Scientific and Technical Research and Innovation Ikerbasque, https://ror.org/01cc3fy72, RF/2023/006 AXA Research Fund, https://ror.org/02zxqxw53
Carbon nanotubes (CNTs) have shown great potential in tissue engineering applications due to their unique properties, namely by improving electrical and mechanical properties of scaffolds. In recent years the use of 3D patterns, specially honeycomb or hexagonal patterns, to improve cell culture environment has also emerged in the tissue engineering field. Here we design HEMA-PEGDA based 3D printable scaffolds with and without CNTs in order to study the effect of both surface pattern and CNT incorporation on electroactive hiPSC-derived neuron and cardiomyocyte differentiation. Firstly, we tested scaffold biocompatibility with the SH-SY5Y neuroblastoma model, observing great viability and scaffold coverage for the CNT-containing formulation. As for the hiPSC differentiation models, we employed calcium signalling, immunocytochemistry and RT-qPCR techniques for cellular characterization. We found that CNTs and surface topography greatly affect neuronal culture maturation, by improving neuronal marker expression, calcium transient amplitude and axonal network maturation, while cardiomyocyte culture was mainly impacted by CNT presence independently of surface structure, although these conditions were not enough to reach full maturity. Overall, this study provided insights into the impact of surface structure and composition in electroactive cell differentiation and maturation. ### Competing Interest Statement The authors have declared no competing interest. Spanish Research Agency, PID2022-140419OB-I00, CNS2024- 154900 European Commission, https://ror.org/00k4n6c32, ERC-2024-POC, grant agreement no. 101213598 Fundación Bancaria Caixa dEstalvis i Pensions de Barcelona, https://ror.org/05r3yzw86, CI23-10375 Spanish National Plan for Scientific and Technical Research and Innovation, RYC2023-043851-I Ikerbasque, RF/2023/006 AXA Research Fund, https://ror.org/02zxqxw53
The significance of the parameters involved in the synthesis of rare-earth metal-organic frameworks (RE-MOFs) has not been studied in depth. Design of experiments (DoE) is used herein to determine the impact of seven synthetic parameters on the yield and surface area of Y-UiO-66 (UiO = University of Oslo). The seven synthetic parameters are evaluated through 16 experiments, leading to a new synthetic procedure for Y-UiO-66 that increases the yield from 33% to 84% while maintaining high crystallinity and surface area. These results show that a simple screening design, using DoE, is useful for the im-provement of MOF synthesis. The new procedure is successfully adapted to scale-up the reaction twenty times, as well as to improve the yield of Ho- and Yb-UiO-66, demonstrating that it can be extended to lanthanoid analogues of UiO-66. The results obtained from the design were used to improve the yield of another RE cluster-based MOF, Tb-CU-27 (CU = Concordia University) with only one experiment, suggesting that the synthetic parameters identified as being significant for Y-UiO-66 have a similar effect on other RE cluster-based MOFs.
Since their introduction into humans, H3N2 influenza A viruses have evolved continuously to escape immunity through antigenic drift, driven by mutations in and around the receptor-binding site. Recently, these changes resulted in viruses that recognize elongated glycans, which are less abundant in the human respiratory tract, complicating vaccine strain propagation. This study employed ELISA, glycan arrays, tissue staining, flow cytometry, and hemagglutinin (HA) assays to demonstrate the molecular determinants of recent H3N2 viruses that regained recognition of shorter glycans. Mutations Y159N/T160I in contemporary strains replace Y159/T160, weakening receptor binding. However, this is compensated by Y195F in the 190-helix. These findings highlight epistasis across critical residues in the HA receptor-binding site, including the 130-loop, 150-loop, and 190-helix. Interestingly, a positive correlation exists between binding to an asymmetrical N-glycan and binding to human and ferret respiratory tract tissues. These results elucidate the epistatic nature of receptor-binding specificity during influenza A virus H3N2 evolution.
